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Destabilization of Microtubules01:45

Destabilization of Microtubules

The destabilization of microtubules can occur during different stages of the microtubule lifecycle, such as nucleation or elongation. It can take place at either end of the microtubule or in the microtubule lattices as a whole. The lifespan of individual microtubules within a cell varies according to the cell type and stage of the cell cycle. During interphase, the lifespan of the microtubule is about 30 minutes, while during cell division, it is about 15 minutes. In axonal microtubules of...
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Microtubules are hollow cylindrical filaments having a diameter of approximately 25 nm and a length that varies from 200 nm to 25 μm. GTP-bound tubulin subunits form αβ-heterodimers for microtubule assembly. These core building blocks interact longitudinally, polymerizing into protofilaments. The protofilaments then interact with one another through lateral bonding forces to form stable cylindrical microtubules. These cylindrical filaments are dynamic as they undergo repeated assembly and...
Microtubule Instability02:17

Microtubule Instability

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Microtubules in Cell Motility01:24

Microtubules in Cell Motility

Microtubules are thick hollow cylindrical proteins that help form the cytoskeleton. Microtubules have varied roles in the cell. These filaments help form cellular appendages like cilia and flagella, which are responsible for locomotion. The cilia arise from basal bodies, separated from the main body by a membrane-like structure forming the transition zone. This zone is the gate for the entry of lipids and proteins, creating a unique composition of lipids and proteins in the ciliary membrane and...
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Microtubules are thick hollow cylindrical proteins that help form the cytoskeleton. Microtubules have varied roles in the cell. These filaments help form cellular appendages like cilia and flagella, which are responsible for locomotion. The cilia arise from basal bodies, separated from the main body by a membrane-like structure forming the transition zone. This zone is the gate for the entry of lipids and proteins, creating a unique composition of lipids and proteins in the ciliary membrane and...
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Cytoskeletal Coordination in Cell Migration

A migrating cell changes its shape during the cyclic events of attachment and detachment from the substratum and repositions the cell organelles correspondingly. These complex events are orchestrated by the dynamic cytoskeletal network comprising actin filaments, intermediate filaments, and microtubules. Cytoskeletal crosstalk — the direct and indirect communication between the different components — is crucial for this coordination. Direct communication involves various linker proteins that...

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STAT3-stathmin interactions control microtubule dynamics in migrating T-cells.

Navin K Verma1, Jennifer Dourlat, Anthony M Davies

  • 1Department of Clinical Medicine, Institute of Molecular Medicine, Trinity College Dublin, Dublin 8, Ireland. verman@tcd.ie

The Journal of Biological Chemistry
|March 3, 2009
PubMed
Summary

Signal transducer and activator of transcription 3 (STAT3) is crucial for T-cell migration. STAT3 activation regulates microtubule dynamics by interacting with stathmin, impacting T-cell locomotion and associated signaling.

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Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • T-cell migration is essential for immune responses and implicated in diseases like chronic inflammation and cancer metastasis.
  • Understanding the regulatory mechanisms of T-cell migration is critical for therapeutic interventions.

Purpose of the Study:

  • To investigate the role of Signal Transducer and Activator of Transcription 3 (STAT3) in integrin-induced T-cell migration.
  • To elucidate the molecular mechanisms by which STAT3 influences T-cell locomotion.

Main Methods:

  • Utilized an established in vitro model for lymphocyte migration using Hut78 T-lymphoma cells.
  • Investigated STAT3 activation and nuclear translocation during T-cell motility induced by LFA-1.
  • Employed methods to block STAT3 signaling and analyzed effects on T-cell locomotion, microtubule stability, and tubulin modification.
  • Examined the physical interaction between STAT3 and stathmin.

Main Results:

  • STAT3 was activated and translocated to the nucleus in Hut78 T-lymphoma cells during LFA-1-induced migration.
  • Inhibition of STAT3 signaling impaired LFA-1-induced T-cell migration by destabilizing microtubules and altering tubulin.
  • Demonstrated a physical interaction between STAT3 and stathmin, regulating microtubule dynamics in migrating T-cells.

Conclusions:

  • STAT3 plays a critical role in regulating T-cell migration.
  • STAT3 signaling is essential for maintaining microtubule stability and dynamics during T-cell locomotion.
  • The interaction between STAT3 and stathmin is a key mechanism controlling T-cell migration.